The objective of this research project is to identify the plasma lipoprotein source of cholesterol utilized by the liver for bile acid synthesis and biliary cholesterol secretion. This is an extension of our ongoing multicompartmental analysis of cholesterol metabolism in man which has shown that plasma free cholesterol is the matter source of the cholesterol present in the hepatic bile acid and biliary cholesterol precursor sites. Previous studies in two bile fistula patients administered HDL and LDL free cholesterol suggested that the major plasma free cholesterol source for the biliary lipids is from HDL. During the past year additional studies have been carried out in both bile fistula patients and subjects with an intact enterohepatic circuit. HDL, LDL and VLDL free cholesterol have been administered in pairs (for example, 3H-HDL and 14C-VLDL free cholesterol). Analysis of the samples is being carried out presently; preliminary results extend the initial finding that HDL, rather than the Apo B containing lipoproteins, is the major plasma source of biliary lipids. In studies just started this year, the isolated perfused swine liver is being used as an experimental model in order to study aspects of lipoprotein free cholesterol transport to the liver which can not be studied in vivo in man. Perfusion of the liver with lipoprotein deficient media results in a gradually decreasing biliary secretion of cholesterol and bile acids with time. Addition of lipoproteins (density less than 1.21) to the media increases biliary secretion of these lipids to above the control levels. Future studies will investigate the effect of individual lipoproteins (LDL or HDL) in the perfusion media on biliary cholesterol and bile acids.